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Indonesian Journal of Medical Chemistry and Bioinformatics

Abstract

The Sodium-Glucose co-transporter-2 (SGLT2) inhibitor represents a novel agent for the treatment of type 2 diabetes. Drugs of this class function by inhibiting glucose reabsorption in the kidneys, thereby controlling blood glucose levels. It is known that SGLT2 inhibitors activate the AMPK signaling pathway by increasing the expression and activity of AMP-activated protein kinase (AMPK). In vivo tests have demonstrated that ethanolic and aqueous extracts of Welsh onion leaves (Allium fistulosum L) can reduce body weight, liver weight, adipocyte size, and enhance AMP-activated protein kinase (AMPK) expression. In this study, the inhibitory activity (IC50) of compounds within Allium fistulosum against SGLT2 was predicted using the Support Vector Regression (SVR) predictive model and the SkelSpheres descriptor. The results of the predicted IC50 measurements for compounds present in the 70% ethanol extract of Allium fistulosum in silico indicate that 4 tyramine derivatives and 1 decursidate compound exhibit Excellent or Potent inhibitor activity criteria (IC50 < 1 µM). Among these, the four tyramine group compounds are the isomers N-trans-feruloyltyramine and N-cis-feruloyltyramine, as well as the isomers N-trans-feruloyl-3'-methoxytyramine and N-cis-feruloyl-3'-methoxytyramine. The findings of this study suggest that the ability of Allium fistulosum to enhance AMPK expression is possibly achieved through the inhibition of SGLT2.

Bahasa Abstract

Inhibitor SGLT2 (Natrium-Glukosa co-transporter-2) mewakili agen baru dalam pengobatan diabetes tipe 2. Obat kelas ini menghambat reabsorpsi glukosa di ginjal, mengontrol kadar glukosa darah. Inhibitor SGLT2 diketahui mengaktifkan jalur sinyal AMPK dengan meningkatkan ekspresi dan aktivitas protein kinase teraktivasi AMP (AMPK). Pengujian in vivo menunjukkan ekstrak etanol dan air daun bawang Wales (Allium fistulosum L) dapat mengurangi berat badan, berat hati, ukuran adiposit, dan meningkatkan ekspresi AMPK. Studi ini memprediksi aktivitas penghambatan (IC50) senyawa dalam Allium fistulosum terhadap SGLT2 dengan model prediksi Regresi Vektor Pendukung (SVR) dan deskriptor SkelSpheres. Hasil prediksi IC50 untuk senyawa dalam ekstrak etanol 70% Allium fistulosum secara in silico menunjukkan 4 derivatif tiramin dan 1 senyawa dekursidat memiliki aktivitas inhibitor Luar Biasa atau Kuat (IC50 < 1 µM). Di antaranya, empat senyawa kelompok tiramin adalah isomer N-trans-feruloyltiramin dan N-cis-feruloyltiramin, serta isomer N-trans-feruloyl-3'-metoksitiramin dan N-cis-feruloyl-3'-metoksitiramin. Temuan studi ini mengindikasikan bahwa kemampuan Allium fistulosum meningkatkan ekspresi AMPK mungkin dicapai melalui penghambatan SGLT2.

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